Exam 2 11/2 Antimicrobial Therapy Flashcards
(131 cards)
1
Q
Previous Exam question
What part of the bacteria is most important to maintain osmotic pressure?
A
Cell wall
Wrong answer is cell membrane
2
Q
Previous exam question
Which cells recognize virally infected cells?
A
CD8/CTL
Recognize MHC I (endogenous antigens, check inside cell)
3
Q
Previous exam question
Which immune cell does both phagocytosis and antigen presentation?
A
Macrophages
Neutrophils do phagocytosis but do not do APC!
4
Q
Narrow Spectrum
A
Limited activity; works against small subset of bacteria
5
Q
Broad spectrum
A
Work against greater variety of bacteria
6
Q
________ agents inhibit bacterial replication
A
Bacteriostatic
7
Q
________ agents kill bacteria
A
Bactericidal
8
Q
Why is it important to consider minimum bactericidal concentration (MBC)?
A
Too many bacteria would be killed, including commensal bacteria (which are good for us and also help to prevent infections)
9
Q
Minimum bactericidal concentration
A
lowest concentration of an antibacterial agent required to kill a particular bacterium
10
Q
What is the goal of antimicrobial chemotherapy?
A
Selective toxicity - can be given to humans with reasonable safety while having toxic effects on specific microorganisms
11
Q
Antibacterial is a broad class of:
A
Antimicrobials
12
Q
Penicillin binding proteins
A
membrane-associated proteins involved in the biosynthesis of peptidoglycan
13
Q
Different bacteria have different _____, which makes them have different susceptibility to beta lactams
A
PBPs
14
Q
Beta lactam antibiotics block active site of ____ in order to prevent ____
A
PBPs, transpeptidase, etc.; cell wall synthesis
15
Q
List the 5 beta-lactam antibiotics
A
- penicillins
- cephalosporins
- cephamycins
- carbapenems
- monobactams
16
Q
Penicillins consist of a beta lactam ring (___-membered ring) bound directly to thiazolidine, a ___ -membered ring
A
4; 5
17
Q
What differentiates various penicillins?
A
Different R groups
(Ex. Penicillin, amoxycillin, etc)
18
Q
True or false: Beta lactam antibiotics are all cell wall inhibitors, but not all cell wall inhibitors are beta lactams
A
True - for example, vancomycin works against cell wall but is not a beta lactam
19
Q
True or false: cephalosporins contain a beta lactam ring
A
True
20
Q
_____ are composed of a beta lactam ring (4M) fused with dihydrothiazine ring (6M)
A
Cephalosporins
21
Q
Which antibiotic is similar to cephalosporins?
A
Cephamycins
22
Q
Cephalosporins and cephamycins are both resistant to:
A
Many beta lactamases
23
Q
Many gram-negatives are now developing resistance via _______________ which is conferred by ___________________
A
- beta-lactamase (bacterial enzymes)
- R (resistance)-plasmid
24
Q
Carbapenems are a broad/narrow spectrum β-lactam antibiotic
A
Broad
25
TEST QUESTION: Monobactams are a broad/narrow spectrum β-lactam antibiotic
Narrow
26
Monobactams are active against ______. ______ and ______ are resistant
Aerobic gram negatives; anaerobes and gram positives
27
What antibiotic is widely used in dentistry?
Penicillins
28
All penicillins share problem of _________
Allergy
29
#1 most reported drug allergy
Penicillin
30
Minor reaction to penicillin that is most common _____; second most common ____
GI upset; rashes
31
True or false: with a penicillin allergy, severe reactions are common such as anaphylaxis and seizure
False - severe reactions are rare
32
_____ of patients are sensitive to penicillin - why?
10%; cross reactivity to cephalosporins and other beta lactam antibiotics
33
What are the ways that bacteria show resistance to beta lactams - which method is most common/easiest?
- block interaction of PBP and antibiotic
- modification of binding
- hydrolysis by beta lactamase (Most common)
34
How many beta lactamases or penicillinases exist that confer resistance to beta lactams?
About 200
35
There are 4 main classes of β-lactamases/penicillinase.
1. What is the most common?
2. Which class is the most resistant?
1. Class A
2. Class C (extended spectrum Beta lactamases)
36
Penicillinases have minimal activity against _______
Cephalosporins
37
What organisms produce Class A beta lactamases?
Gram-negative rods, Escherichia, Klebsiella
38
B-lactamase inhibitors
- clavulanic acid
- sulbactam
- tazobactam
39
Augmentin
Clavulanic acid + amoxicillin
(blocks penicillinase and transpeptidase)
40
Pharmacokinetics - what is bioavailability
A measure of the extent of drug absorption for a given drug and route (from 0% to 100%)
41
Penicillins and cephalosporins: excretion
Renal (mostly unchanged > 80%)
Half life 30-90 min
42
Vancomycin works against what bacteria
Streptomyces orientalis
43
Vancomycin has a different mechanism way of inhibiting cell wall formation, instead of disrupting the β-lactam ring it binds:
Terminal D-ala-D-ala residues on gram-positive organisms
44
Some bacteria (Lactobacillus, Enterococcus faecalis) have Intrinsic resistance to Vancomycin: instead of D-ala-D-ala residues at the terminus they have
D-alanine-D-serine
45
True or false: MRSA have acquired resistance to vancomycin and are now VRSA
True - plasmid genes confer VanA and VanB
46
Bacitracin is a _____ inhibitor and is effective against
polypeptide cell wall inhibitor; gram-positive - blocks bactoprenol
47
Vancomycin is a _____ inhibitor
Glycopeptide cell wall inhibitor
48
Bacitracin should be applied as ____ only
Topical
Should not be ingested because it blocks enolase
49
Polymixin is a _____ inhibitor
Polypeptide cell wall inhibitor
50
Polymixin disrupts ____ so it is effective against gram-negative bacteria
LPS
51
Polymyxin is _____________ so it is mainly for topical use
Excretion is _____________
nephrotoxic; renal
52
Isoniazid is a ______ inhibitor
Mycobacteria cell wall inhibitor
53
Ethionamide is a derivative of
Isoniazid
54
Isoniazid blocks synthesis of:
Mycolic acid
(works against Mycobacteria tuberculosis)
55
Ethambutol is a _____ inhibitor
Mycobacteria cell wall inhibitor
56
Ethambutol blocks:
Arabinogalactan synthesis (cell wall)
57
Cycloserine is a _____ inhibitor
Mycobacteria cell wall inhibitor
58
Cycloserine inhibits:
Other cell wall synthesis enzymes like D-alanine-D-alanine synthetase and alanine racemase
59
Alanine racemase is used in:
Mycolic acid synthesis
60
Isoniazid excretion and metabolism
Excretion - renal
Metabolism - hepatic (50-90%)
61
____ has a bimodal half life depending on ____.
50% of black and white individuals have a ____ half life, whereas 90% asians/Inuits have a ____ half life.
Isoniazid; race; Longer (3 hour); Shorter (1 hour)
62
Name the cell wall inhibitors that work against mycobacteria
Isoniazid, Ethionamide, Ethambutol, Cycloserine
63
Aminoglycosides are _____ inhibitors
Protein synthesis
64
Protein synthesis inhibitors (7)
- aminoglycosides
- tetracyclines
- macrolides
- chlorampenicol
- clindamycin
- streptagramins
- fusidic acid
65
Streptomycin is a(n) _____
Aminoglycoside
66
Aminoglycosides bind irreversibly to ____
30S ribosome
67
Aminoglycosides are effective against ____ bacteria, but ____ are generally resistant
Aerobes; anaerobes
68
Aminoglycosides are toxic to:
Ear and kidney
Ototoxicity.Chochleotoxicity
69
Tetracyclines are _____ inhibitors
Protein synthesis (30S)
70
Tetracyclines spectrum
Broad spectrum
71
Tetracyclines should be avoided in which people?
Children under 8 years old
Pregnant/lactating women
72
Those who have received tetracycline treatment may develop:
Unsightly tooth staining
73
Linezolid is used to treat:
Penicillin and vancomycin resistant staphylococci, streptococci, enterococci
74
Erythromycin, azythromycin, and clarithromycin are:
Macrolides
75
Macrolides are _____ inhibitors
Protein synthesis (50S)
76
Linezolid is a _____ inhibitor
Protein synthesis inhibitor
77
First choice for penicillin allergic patients?
Macrolides (erythromycin)
78
Chloramphenicol binds:
50S ribosome
79
Chloramphenicol cannot be given in high doses or for a long time because:
They cause bone marrow aplasia (toxic)
80
Clindamycin binds
50S ribosome
81
Which antibiotic can treat VRSA and VRE (vancomycin resistant S. aureus/enterococcus)?
Streptagramins
82
Streptagramins bind
50S
83
Fusidic acid blocks what ribosome
50S ribosome
84
Erythromycin has contraindications with:
Liver disease (hepatitis)
85
Erythromycin metabolism and excretion
Hepatic (>95%), bile
86
Nucleic acid inhibitors (3)
- metronidazole
- quinolones
- rifampin
87
Is metronidazole bacteriostatic or bactericidal?
Bactericidal
88
Metronidazole blocks _____ in all _____
DNA synthesis; strict anaerobes
89
Rifampin blocks:
RNA polymerase (inhibits RNA synthesis)
90
If you need to treat mycobacteria resistant to Isoniazid, you can prescribe:
Rifampin
91
Rifampin is bactericidal/bacteriostatic? It is very active against _____
Bactericidal; aerobic, gram-positive cocci
92
Rifampin increases p450 CYP enzymes, which increase clearance for ____ (contraindication)
anti-HIV medications
93
Someone with HIV and has Mycobacteria, they would likely be taking Isoniazid and anti-HIV drugs so they cannot be given ____
Rifampin
94
Quinolones/fluoroquinolones inhibit
DNA gyrases/topoisomerases --> inhibit DNA replication
95
Anti-metabolites (2)
- sulfonamides
- trimethoprim
96
Sulfonamides inhibit ______. Poses potential complications with ____
Folic acid synthesis; pregnancy
97
Folic acid is needed to make
Purines and pyrimidines (Dna synthesis)
98
Trimethoprim inhibits ______ and is contraindicated in ____
dihydrofolate reductase; pregnancy
99
Why is antibiotic resistance a problem in dentistry?
Oral bacteria (streptococci) may develop cross resistance to both penicillins and cephalosporins
100
_____ rapidly acquires resistance while ____ rarely do so
S. aureus; S. pyogenes
101
Resistance to some antibiotics like ____ is virtually unknown, whereas strains resistant to other drugs like ____ readily emerge
Metronidazole; penicillin
102
Methicillin is relatively resistant to:
beta-lactamases
103
Almost all S. aureus is sensitive to ____. However, ___ is emerging so vancomycin must be used instead. However, reports of ____ are not detected so linezolid or streptogramins must be used instead
Methicillin; MRSA; VRSA
104
Types of resistance
- primary (intrinsic) resistance
- acquired resistance
- cross-resistance
105
Order of operation for antibiotic prescribing
1. Penicillin
2. Methicillin
3. Vancomycin
4. Linezolid
5. Streptagramins
106
Primary (intrinsic) resistance
- naturally resistant to the drug
- vancomycin ineffective in D-alanine-D-serine bacteria
107
Acquired resistance
- mutation or gene transfer
- Rifampin ineffective against RNA polymerase mutation
- beta lactamase transfer (R-plasmid)
108
Cross-resistance
- resistance to one drug confers resistance to related drugs (R-plasmids)
- penicillin and cephalosporin resistance
109
Mechanisms of resistance
1. altered target - lower affinity for antibacterial but still functional
2. altered uptake - increasing impermeability or increased efflux of drug out of cell
3. drug inactivation - enzymes which modify or destroy the antibacterial agent
110
Only documented plasmid to transfer in free-living environments
NDM-I (superbug)
111
KPC
Klebsiella pneumoniae carbapenemase (superbug, ESBL)
112
Four main treatments to reduce rejection of transplant
1. methotrexate
2. cyclosporin
3. tacrolimus
4. glucocorticoids (prednisone)
113
Methotrexate (MTX) is often used in
chemotherapy and autoimmune disorders
114
Methotrexate competitively inhibits
Dihydrofolate reductase (DHFR)
115
Methotrexate inhibits ____ binding
IL-1 beta
116
IL-1
inflammation
117
Pharmacologic immunosuppression can present ____ and treat _____
graft vs host disease (GVHD); autoimmune disease
118
Methotrexate is a treatment for
GVHD, autoimmune disorders (decreases inflammation)
119
What drugs interact with methotrexate?
1. penicillin (decreases elimination of MTX which can kill them)
2. aminoglycosides (reduce absorption of MTX)
3. NSAIDs have potentially fatal interactions
4. nitrous oxide induces hematologic toxicity of MTX
120
Cyclosporins are mainly used to treat ____ and prevent ____
Autoimmune diseases; GVHD
121
Cyclosporin inhibits?
IL-2 and T-lymphocyte activity
122
Tacrolimus interacts with
Macrolides
123
Tacrolimus inhibits ____ production
IL-2
124
Which is a more potent immunosuppressant - tacrolimus or cyclosporin?
Tacrolimus
125
Tacrolimus is used to treat/prevent:
autoimmune disease; GVHD
126
What drugs have contraindications with tacrolimus?
1. macrolides (erythromycin)
2. azoles )fluconazole)
127
Tacrolimus is nto used with what patients?
Hep B/C patients
128
Tacrolimus competed for:
CYP3A - cytochrome P450 liver enzymes
129
Tacrolimus is influenced by _____. _____ make non-functional CYP3A5 protein, increasing risk of drug toxicity
Genetics; CYP3A5 G/G
130
Glucorticoids (prednisone) treats _____; what effects does it have
Overactive immune diseases (high doses = immunosuppression)
- may result in T-cell or humoral immune deficiency, neutropenia
131
Glucocorticoids inhibit what cytokines?
IL-1, IL-2, IL-4, IL-6, IL-8
